Preparation of acyloxy carboxylic acids from esters of hydroxy carboxylic acids



Patented Aug. 15, 1950 T;..UN,ITED {STATES I. PREPARATION, OF ACYLOXY'CARBOXYLIC ACIDS FROM ESTERS OF HYDBOXY'CAR- BOXYLIC ACIDS MartinL.--Fein, Riverside, N.J.,and Charles H.

tary" of Agriculture Fisher, Abington, Pa., assignors to the UnitedStates of America as represented by the Secre- No Drawing. ApplicationApril 19,1946,

. 1 SerialNo. 663,337

9.Claims. (C1.260484) (Granted under ,the act of March 3; 1883, as

' This application is made under the act of March 3, 1883, asamended-bythe act-of April 30, 1928, and the invention herein described,if patented, may be manufactured and used by or for the Grovernment ofthe United States of America for governmental purposes without thepayment to us of any royalty-thereo-n; 3 This invention relates tothe'productionof acyloxy I carboxylic acids iby. the interaction ofhydroxy estersandcarboxylic acids-and, inparticular, to the productionof lower saturated aliphatic acyloxy (including halogen-substitutedacyloxy) mono-carboxylic acids, such as alphaacetoxypropionic acid,acetoxyacetic acid, alphaacetoxyisobutyric acid, chloroa'cetoxypropionicacid, andalpha-propionoxypropionic acid, and the simultaneous productionof valuable auxiliary esters and acyloxy esters: of lower saturatedaliphatic carboxylic acids, and has, among its objects, the obtaining ofthese products in a simple and efficient manner. V Th'eproducts obtainedaccording totheinvention are valuable as such formany purposes'and areuseiul intermediatesin the productiono'f solvents, plasticizers, resinintermediates; insecticides, andins ectrepellents? "f In general,accordingtothe invention, ahydroxy ester, in particular, an ester of alower; saturated, aliphatic alpha-hydroxy mono-carboxylic acid havingthe formula RCR'OI-ICOOR.

Where R and R are H or a lower alkyl, such as Cid; or CI-IsCI-Iz, and Ris an estergroup, is mixed withan excess of a lower,saturated,

aliphatic mono-carboxylic acid, including lower,

halogen substituted aliphatic mono-carboxylic acids'having the formula kV V RWCOOH 3 ,where ER is H or a lower alkyl or halogen substitutedalkyl, such as CH3, .CHaCHz, and CH2C1,

with an entraining agent and with an acid catal'yst. {lhe reactionmixture is heated, and the water fprmed in the reaction is removed witha part ofgthe entraining agent by distillation dur-- ing the reaction.The remaining ent'raining agent i and excess reacting acid are thendistilled, following which the formed acyloxy acid and formed acyloxytester, each corresponding to the ester used and with its acyloxy groupderived from the amended April"30, 1928; 370 O. G. 757) Other formedauxiliary esters may be distilled at suitable conditions of temperatureand pressure or may be recovered from prior distillates.

Example -I exhibits the invention in greater detail.

Escample I One mole of methyl lactate, 6 moles of acetic acid, 200ml ofbenzene (as the entraining agent) and 0.5 ml. of concentrated sulfuricacid (as the catalyst) were placed ina one-liter, round-bottom flask,fitted with a thermometer through a 10 mm. internal diameter side arm.The flask,

was attached to a 2 l-inch Vigreux column (ap-' proximately '20 inchesindented) well wrapped with asbestos insulation. The top of the columnwas fitted with a modified Barrett moisture trap (either plain or watercooled) above which was;

placed acondenser. The flask was heated with a 550-watt electric heateroperating at 70 volts..

llowevenother methods of heating may be used. Refiuxing was carried outat 91-93? C. (tem-- perature of reaction mixture) for approximatelythermometer in the flask was replaced by a capillary tube for use duringthe vacuum distillation. Benzene and excess acetic acid were removedundervacuum supplied by a simple water'pump.

'Methyl alpha-acetoxypropionate in a yieldof 1.4091 for the yellowsodium line at 20 C., and

, alpha-acetoxypropionic acid in a yield of 0.51

mole, having aboiling point of 75 to 79 C. at"

0.1 mm. Hg and a refractive index of 1.4240 for driven pump.

'The above-described experiment was repeated on a larger scale usingtoluene as the entraining agent, and the distillate was collected andexam-' ined, The distillate was found to contain the en-; t trainingagent, water, and methylacetate, the latare recovered from the residueby distillation at lower temperatures and/orlower pressures. l

ter being obtained in high yield.

Variations in the procedure of Example I may be made. Toluene, isopropylacetate, ethylene chloride, methylene chloride, Skelly solve B(essentially n-hexane, boiling range, 63 to C.)

cyclohexane, or other entraining agents may be substituted for benzene,some of which will result in a'somewhat higher yield of the formedacidand lower yield of the formed ester.

Also, the excess of reacting acid may bevariedover it Wide range withoutappreciable eifects Table 1 Yield of formed Products, moles 001101.11?n1 1 1 h .1119 y a D a-.

pionate P P 0. 1 0. 53 1 2 o. 51 0. 2s 0. 3 o. 45 0. 33 4 0. 31 44 0. 50. 35 0 51 0.6 o. 22 0. 59. o. 7 0. 0. 63' 0.28 0.57 0 o. 21 0. 57

Although this invention'is primarily concerned with the production ofalpha-acetoxypropionic acid and the auxiliary ester, methylalphaacetoxypropionate, other acyloxy carboxylic acids andauxiliaryesters may be produced by following theprocedure of Example 1, exceptfor substituting other reacting esters and other reacting carboxylicacids, and, of course; adjusting the distillationtemperatures properlyto recover the formedproducts; Such are exhibitedin Table 2 ifrwhich"the procedure of Example I is followed.

,4 The refractiveindex mil andi melting points of the products obtainedin the various examples are given in Table 3.

Table 3 Product acetoxyacetic acid aloha-acetoxyisobutyric acid;chloroacetoxypropionic. acid acetoxypropionic acid. propionoxy propionicacid ethylalphaacetoxypropion isob'utyl a1 pha-acetoxyprop on aren-butyl alpha-acetoxypropionate isopropyl alpha-acetoxypropionatetetrahydrofurfuryl alpha-acetoxypropionate methyl acetoxyacetntisobutyl-acetoxya sec.-buty1 acetoxya cefa methylalpha-acetoxyisobutyrate; ethyl-alpha-acetoxyisobutyrate 1. 4125 ethylformoxypropionate. ethyl chloroacetoxypropionate; methyl propionoxypro iAlthoughtheabovev examples disclose sulfuric. acid as the catalyst,other. acids,.such.as sulfonic acidmay be.used. Also, the reactants maybe dissolved. :in .amutualsolvent, if desired.

Having thus described our. invention, we claim:

1..A process comprising mixing an ester of a.

lower,.saturated, aliphatic alpha-hydroxy monocarboxylic acidlwithanexcess of a lower,.saturated,- aliphatic mono-carboxylic acid, with anentraining. agent, and Withan acid catalyst, heatingthereactionrmixture, removing formed water: and the entraining agent.during the reaction by distillation, and recoveringfrom the residue-theformed acyloxy acidwhich corresponds to. the reacting ester with itsacyloxy group derived from the reacting acid.

2. Theprocess of .claim .1, inv which the reactexcept that'in ExampleXI, 0.8 ml. of conceningesterisa lactate,.and.the reacting acid istratedI-I2SO4 was used instead of 0.5 ml. and inacetic acid. ExampleXIV, 0.5 mole of ethyl lactate and 3 3..The.process-of.claim 1, in.which the reactmolesofchloroaceticacid were usedinstead'of' 1 ing esteris a lactate, and the reacting acid is a mole-'andfi moles;respectively. halogenesubstituted.acetic acid.,

Table 2 Reactonts Products obtained, yields and characteristics" Ex--Acid E ter ample Ester Acid T Yield, B. P., P.'mm. Yield, B. P., P. mm.Mole 01 Eg Mole 0. Hg.

IL. -ethyllactate .acetic. alpha-acetoxypropi- 0.50 -79 0; 1' ethylalpha-acetoxy- 0. 38 91 28.0

L onic; propionate. :isobutyllactatm... do do 0.35 isobutyl .alpha-ace-0.45 74 5.3 toxypropionate. IV..- n-butyllactatedo do 0.28.n-butylalpha-acetoxy- 0.55v 105.

propionate. V. 1sopropy1lactate do dn 0.17 isopropyl alpha-acet- 0.66 7713. 4.

oxypropionate. 1 13.- tetrahydrofu'rfuryl do do tetrahydroiurfuryl 9.1-0.46 3;.2

lactate.. pha acetoxypropio V nate. VII; 'mezhtyl hydroxy ac doacetoxyacetic; 0.50 78 0.4 methylacetoxyacetate- 0.31 173-174 760.13;

7 e a e. VIII; isolzuttylhydroxyacdo do 0.43 isobvityl acetoxyace- 0.4961-62 2.0

I e a e. a e. IX. sec.-buty1 hydroxy do do 0.10 sec.butylacetoxyace--0:68.. 53 0.7

acetate. ta XL- methyl alpha-hydo alpha-acetoxy' iso- 0.29 79- 0.2methylalpha-acetoxy- 0;45 67=-69 16.8

droxylsobutyrate. butyric. isobutyrate. XI..- 'ethylalpha-acetoxy- 7 dodo 0.19 ethyl alpha-acetoxy: 0.47 74 14.6 lsobutyrate' isobutyrate. XIL-dn dn do dn 0.51 X11!- ethyl lactate. formic ethyl formoxypropio- 0.3391 1.2

nate. X -d0 chloroacetic. chloroacetoxy pro- 0.19 113-118 0.4 ethylchloroacetoxy' 0.23 69-71 0.6

pionic. propionate. XV; methyllactate propionic propionoxypropion- 0.4786-89 0.8 methyl propionoxy 0.35 70 9.9

ic. V propionate. XVL beta-butoxy-ethyl aceticacid beta-butoxyethylal-0.55 -121 5 lactate." phat-acetoxyrpropiona c.

4. The process of claim 1, in which the reacting ester is a lactate, andthe reacting acid is propionic acid.

5. A process comprising mixing an ester of a lower, saturated, aliphaticalpha-hydroxy monocarboxylic acid with an excess of a lower, saturated,aliphatic mono-carboxylic acid, with an entraining agent, and with anacid catalyst. heating the reaction mixture, removing formed water andthe entraining agent during the reaction by distillation, and recoveringfrom the residue the formed acyloxy acid and formed acyloxy ester, eachcorresponding to the reacting ester and with its acyloxy group derivedfrom the reacting acid.

6. A process comprising mixing methyl lactate with an excess of aceticacid, with an entraining agent, and with an acid catalyst, heating thereaction mixture, removing formed water, the retraining agent and formedmethyl acetate during the reaction by distillation, recovering themethyl acetate from the distillate, and recovering from the residue theformed methyl alpha-acetoxypropionate and formed alpha-acetoxypropionicacid.

7. The process of claim 6 characterized in that the heating is continuedfor about 5 hours.

8. A process of simultaneously producing methyl alpha-acetoxypropionateand alpha-acetoxypropionic acid comprising mixing methyl lactate with anexcess of acetic acid, with an entraining agent, and with from 0.1 to1.0 ml. of concentrated H2SO4 per mole of methyl lactate, the largerquantity of the H2S04 being used to produce the larger yield of thealph'a-acetoxypropionic acid, heating the reaction mixture, re-

moving formed water, the entraining agent and formed methyl acetateduring the reaction by distillation, and recovering from the residue theformed methyl alpha-acetoxypropionate and formed alpha-acetoxypropionicacid.

9. Process for the manufacture of alpha-acyloxy lower aliphaticmonocarboxylic acids comprising heating a lower alkyl ester of analphahydroxy lower aliphatic monocarboxylic acid with an excess of alower aliphatic monocarboxylic acid with a liquid water-entraining agentin the presence of an acid catalyst, removing formed water and thewater-entraining agent during the reaction by distillation andrecovering the alpha acyloxy lower aliphatic monocarboxylic acid.

MARTIN L. FEIN. CHARLES H. FISHER.

REFERENCES CITED The following references are of record in the file ofthis patent:

UNITED STATES PATENTS Number Name Date 2,107,202 Lock Feb. 1, 19382,158,107 Carruthers May 16, 1939 2,265,946 Loder Dec. 9, 1941 2,355,971Hansley Aug. 15, 1944 OTHER REFERENCES Fein et al.: Ind. and Eng. Chem.,vol. 36 (1944), pages 235-238.

Filachione et al.: Ind. and Eng. Chem, vol. 36 (1944), pages 472-475.

1. A PROCESS COMPRISING MIXING AN ESTER OF A LOWER, SATURATED, ALIPHTICALPHA-HYDROXY MONOCARBOXYLIC ACID WITH AN EXCESS OF A LOWER, SATURATED,ALIPHATIC MONO-CARBOXYLIC ACID, WITH AN ENTRAINING AGENT, AND WITH ANACID CATALYST, HEATING THE REACTION MIXTURE, REMOVING FORMED WATER ANDTHE ENTRAINING AGENT DURING THE REACTION BY DISTILLATION, AND RECOVERINGFROM THE RESIDUE THE FORMED ACYLOXY ACID WHICH CORRESPONDS TO THEREACTING ESTER WITH ITS ACYLOXY GROUP DERIVED FROM THE REACTING ACID.